Left untreated, HIV (human immunodeficiency virus) can progress to AIDS (acquired immune deficiency syndrome). The immune deficiency is caused by the loss of special white blood cells, called CD4 or "T" cells, which are essential for the body to defend itself against infectious diseases.
"Liver disease is one of the major causes of illness in HIV-infected patients who also have hepatitis C," says Kenneth Sherman, MD, PhD, director of the UC College of Medicine's digestive disease division and principal investigator of the trial. "More than a million Americans have HIV and 25 percent of those also have hepatitis C."
In what is known as highly active antiretroviral therapy (HAART), three or more antiviral medications such as efavirenz, tenofovir and emtricitibine are taken in a combination as a treatment for HIV and AIDS. Currently, about 20 different HIV antiviral agents are available in four different drug classes. Patients must take the different pills, as many as 10 a day, at different times and stick to a strict schedule, taking each of the different types and numbers of pills at the same time every day. The success of this triple-drug combination cocktail lies in its ability to disrupt HIV at different stages of its replication.
However, says Dr. Sherman, "In patients with both HIV and hepatitis C, as the HIV virus declines, we often see a simultaneous worsening of hepatitis C and detect abnormal results in blood tests that measure liver function.
"This study will attempt to determine whether liver damage is coming from the HIV medications or from the hepatitis virus itself," Dr. Sherman explains.
Although the liver is the only organ that can regenerate itself, if damage becomes too severe the patient could die or need a liver transplant. As a result, many physicians discontinue the HIV cocktail as soon as they see significant abnormalities in the liver function measured by simple blood tests.
Unfortunately, as soon as an HIV patient quits taking the cocktail of medications, the HIV virus rebounds. "But it's not known whether it's the hepatitis C virus or the anti-viral cocktail that does the damage," Dr. Sherman says.
"Through this study we hope to change how clinicians react to blood test results showing abnormal liver function and a decreased HIV viral load, and in doing so improve HIV/hepatitis C patients' chances of fighting these viral infections," Dr. Sherman says.
Results of a previous study coauthored by Dr. Sherman, published in 2004 in the New England Journal of Medicine, showed that some HIV patients could be cured of accompanying hepatitis C.
"The trick is to control the chronic viral infections without doing irreparable harm to the liver," Dr. Sherman says. "You can live with one kidney or one lung but, as the old saying goes, your liver is your life."
About 30 patients with both HIV and hepatitis C who are taking the standard cocktail treatment will be enrolled in the five-year study at UC and New York University School of Medicine. The patients and their referring physicians will be asked to select one of two initial treatment regimens-either efavirenz plus a fixed dose combination of tenofovir/emtricitibine or atazanzavir with tenofovir/emtricitibine. Efavirenz and atazanavir are manufactured by Bristol-Myers Squibb. The tenofovir/emtricitibine combination is manufactured by and provided at no cost by Gilead Pharmaceuticals.
Joining Dr. Sherman in the study will be Tarek Shata, MD, PhD, Jason Blackard, PhD, and Judith Feinberg, all at UC, Edmund Bini, MD, New York University School of Medicine, and Alan Perelson, PhD, a theoretical mathematician at the Los Alamos National Laboratory in New Mexico.
The researchers have no financial interest in Gilead Sciences, which has agreed to provide drugs for this study.